1. Field
Provided is a p16 protein variant; a polynucleotide encoding the p16 protein variant; a method for preparing the p16 protein variant; a pharmaceutical composition comprising the p16 protein variant; and a method for preventing and/or treating cancer comprising administering the p16 protein variant to a subject.
2. Description of the Related Art
p16INK4a (hereinafter abbreviated as “p16”) plays an important role in cell cycle regulation by decelerating the cell-cycle progression from the gap one phase (G1) to the DNA synthesis (S) phase (i.e., G1→S), a major check point (restriction point) responsible for the division of both normal and cancer cells. More specifically, p16 protein binds to cyclin-dependent kinase 4/6 (Cdk4/6) to arrest cell proliferation (see, FIG. 1).
When p16 protein binds to Cdk4/6, the cell cycle progression from G1 phase to S phase (G1→S) is restricted, which, in turn, prohibits the subsequent events for cancer development including DNA synthesis in S phase and infinite cell division. Therefore, p16 protein can be effectively used as a tumor suppressor.
For cancer therapy using p16, delivery into cancer cells requires modification to provide a recombinant p16 with improved cell membrane permeability. However, human p16 protein is difficult to produce on a mass scale in E. coli because it is expressed as an insoluble form in E. coli. Solubility of p16 may be increased by fusion with GST. However recombinant GST-p16, although expressed and/or isolated, becomes unstable and undergoes precipitation (Byeon, I. J. et al., 1998. Mol. Cell 421-431).
Thus, there is a need for a p16 protein variant with improved solubility that retains affinity for Cdk4/6, to provide for the effective application of p16 in cancer therapy.